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Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea

Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial ce...

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Detalles Bibliográficos
Autores principales: Mussi, Natalia, Stuard, Whitney L., Sanches, Jose Marcos, Robertson, Danielle M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406817/
https://www.ncbi.nlm.nih.gov/pubmed/36010643
http://dx.doi.org/10.3390/cells11162567
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author Mussi, Natalia
Stuard, Whitney L.
Sanches, Jose Marcos
Robertson, Danielle M.
author_facet Mussi, Natalia
Stuard, Whitney L.
Sanches, Jose Marcos
Robertson, Danielle M.
author_sort Mussi, Natalia
collection PubMed
description Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial cells were cultured in a defined growth medium containing 6 mM glucose. To simulate hyperglycemia, cells were cultured in a medium containing 25 mM D-glucose, and control cells were cultured in mannitol. Using metabolic flux analysis, there was a hyperosmolar-mediated increase in mitochondrial respiration after 24 h. By day 5, there was a decrease in spare respiratory capacity in cells subject to high glucose that remained suppressed throughout the 14-day period. Although respiration remained high through day 9, glycolysis was decreased. Mitochondrial respiration was decreased by day 14. This was accompanied by the restoration of glycolysis to normoglycemic levels. These changes paralleled a decrease in mitochondrial polarization and cell cycle arrest. Together, these data show that chronic but not acute hyperglycemic stress leads to mitochondrial dysfunction. Moreover, the hyperglycemia-induced loss of spare respiratory capacity reduces the ability of corneal epithelial cells to respond to subsequent stress. Compromised mitochondrial function represents a previously unexplored mechanism that likely contributes to corneal complications in diabetes.
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spelling pubmed-94068172022-08-26 Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea Mussi, Natalia Stuard, Whitney L. Sanches, Jose Marcos Robertson, Danielle M. Cells Article Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial cells were cultured in a defined growth medium containing 6 mM glucose. To simulate hyperglycemia, cells were cultured in a medium containing 25 mM D-glucose, and control cells were cultured in mannitol. Using metabolic flux analysis, there was a hyperosmolar-mediated increase in mitochondrial respiration after 24 h. By day 5, there was a decrease in spare respiratory capacity in cells subject to high glucose that remained suppressed throughout the 14-day period. Although respiration remained high through day 9, glycolysis was decreased. Mitochondrial respiration was decreased by day 14. This was accompanied by the restoration of glycolysis to normoglycemic levels. These changes paralleled a decrease in mitochondrial polarization and cell cycle arrest. Together, these data show that chronic but not acute hyperglycemic stress leads to mitochondrial dysfunction. Moreover, the hyperglycemia-induced loss of spare respiratory capacity reduces the ability of corneal epithelial cells to respond to subsequent stress. Compromised mitochondrial function represents a previously unexplored mechanism that likely contributes to corneal complications in diabetes. MDPI 2022-08-18 /pmc/articles/PMC9406817/ /pubmed/36010643 http://dx.doi.org/10.3390/cells11162567 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mussi, Natalia
Stuard, Whitney L.
Sanches, Jose Marcos
Robertson, Danielle M.
Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title_full Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title_fullStr Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title_full_unstemmed Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title_short Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
title_sort chronic hyperglycemia compromises mitochondrial function in corneal epithelial cells: implications for the diabetic cornea
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406817/
https://www.ncbi.nlm.nih.gov/pubmed/36010643
http://dx.doi.org/10.3390/cells11162567
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